Metabolic Differences of an Oral and Intravenous Dose of 3-hydroxybutyrate (3-OHB).

An open-labeled intervention study testing healthy, lean, and male volunteers on two separate occasions:

1. blood sampling after consuming 36 gram 3-Hydroxybutyrate (3-OHB) salt.
2. blood sampling while given a variable rate of 3-OHB salt intravenously to replicate the concentrations seen during oral consumption.

The primary outcome is differences in insulin concentrations (incremental AUC) 180 minutes after 3-OHB consumed orally vs. intravenously.

Secondary outcomes includes iAUC for other gastrointestinal hormones and substrates (Glucagon, GLP-1, GIP, glucose, and 3-OHB) Gastric emptying will be evaluated using 1500 mg Paracetamol consumption before each intervention day. Urine will be analyzed for ketone concentrations/excretion rates.

Study Overview

• Status: Completed
• Conditions: Healthy; Incretin Effect; Ketosis
• Intervention / Treatment: Dietary supplement: 3-OHB salt (NaCl)

Detailed Description

An open-labeled intervention study testing healthy, lean, and male volunteers on two separate occasions with at least 48 hours apart.

1. blood sampling after consuming 36 gram 3-Hydroxybutyrate (3-OHB) salt.
2. blood sampling while given a variable rate of 3-OHB salt intravenously to replicate the concentrations seen during oral consumption.

The primary outcome is differences in insulin concentrations (incremental AUC) 180 minutes after 3-OHB consumed orally vs. intravenously.

Secondary outcomes includes iAUC for other gastrointestinal hormones and substrates (Glucagon, GLP-1, GIP, glucose, and 3-OHB) Gastric emptying will be evaluated using 1500 mg Paracetamol consumption before each intervention day. Urine will be analyzed for ketone concentrations/excretion rates.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Department of Diabetes and Hormone Diseases (DoH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• healthy
• 19<BMI<30
• written og oral consent
• No allergies to paracetamol

Exclusion Criteria:

• Chronic disease or daily medical treatment
• Daily intake of ketones or ketogenic diets
• Speaks and understands Danish
• Screening blood sample abnormalities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 3-OHB orally; 36 gram 3-OHB salt consumed orally	Dietary supplement: 3-OHB salt (NaCl); 36 gram 3-OHB salt diluted in 500 ml sterile water
ACTIVE_COMPARATOR: 3-OHB intravenously; Variable amounts of 3-OHB salt given i order to replicate the same individual plasma concentrations measured during the experimental arm.	Dietary supplement: 3-OHB salt (NaCl); 36 gram 3-OHB salt diluted in 500 ml sterile water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
plasma insulin	incremental area under the curve (iAUC) for plasma insulin concentrations {pmol/l}	180 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Glucagon	iAUC and concentrations of (Glucagon {pg/ml}	180 minutes
Gastric emptying	Paracetamol test, 1500 mg following interventions and measuring plasma paracetamol {micromol/l}	180 minutes
Urine 3-OHB	Excretion rates {gram/hour} will be estimated as = urine output {L} x urine 3-OHB concentration {mmol/l} x 0.1041 {g/mmol}/180 minutes	180 minutes
Plasma GLP1	iAUC and concentrations of GLP-1 {pmol/l},	180 minutes
Plasma GIP	iAUC and concentrations of GIP {pmol/l},	180 minutes
Plasma glucose	iAUC and concentrations of glucose {mmol/l},	180 minutes
Plasma free fatty acids	iAUC and concentrations of free fatty acids {mmol/l},	180 minutes
Plasma 3-OHB	iAUC and concentrations of 3-OHB {mmol/l})	180 minutes
Plasma Ghrelin	iAUC and concentrations of Ghrelin {ng/l})	180 minutes
Plasma PYY	iAUC and concentrations of PYY {pg/ml})	180 minutes
height	height {meters}	at time 0 minutes
weight	weight {kg}	at time 0 minutes
BMI	Body mass index = weight/height^2	time 0 minutes
Blood pressure	Arm blood pressure	time 0 minutes and 180 minutes
Satiety questionnaire (Blundell et al. 2010)	VAS/NRS-score of hunger, fullness, satiety, desire, and prospective consumption	At 0, 60, 120, and 180 minutes
Ad libitum food intake	gram (and kcal) intake of an ad libitum meal (sandwich)	at time = 180 minutes

Collaborators and Investigators

• Sponsor: University of Aarhus

Publications and helpful links

General Publications

• Rittig N, Svart M, Thomsen HH, Vestergaard ET, Rehfeld JF, Hartmann B, Holst JJ, Johannsen M, Moller N, Jessen N. Oral D/L-3-Hydroxybutyrate Stimulates Cholecystokinin and Insulin Secretion and Slows Gastric Emptying in Healthy Males. J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa483. doi: 10.1210/clinem/dgaa483.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 7, 2019
• Primary Completion (ACTUAL): November 1, 2019
• Study Completion (ACTUAL): March 1, 2020

Study Registration Dates

• First Submitted: April 29, 2019
• First Submitted That Met QC Criteria: May 1, 2019
• First Posted (ACTUAL): May 2, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 3, 2020
• Last Update Submitted That Met QC Criteria: November 2, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis; Ketosis
• Other Study ID Numbers: 1-10-72-56-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No